REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer.
REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer.
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DOI：
10.3892/ijmm.19.3.363
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发表时间：
2007-03
影响因子：
5.4
通讯作者：
R. Tanimoto;F. Abarzúa;M. Sakaguchi;M. Takaishi;Y. Nasu;H. Kumon;N. Huh
中科院分区：
文献类型：
--
作者：
R. Tanimoto;F. Abarzúa;M. Sakaguchi;M. Takaishi;Y. Nasu;H. Kumon;N. Huh
人类睾丸癌对化疗和放疗非常敏感，被认为是一种可治愈的癌症。癌症在年轻的生殖一代中普遍存在，睾丸功能障碍通常被视为一种副作用，仍然是一个严重的挑战。在本研究中，我们研究了基于REIC/Dkk-3的基因治疗对人类睾丸癌的潜在效用。REIC/Dkk-3的表达在所有的人生殖细胞瘤和非生殖细胞瘤组织中均降低。使用腺病毒载体（Ad-REIC）过表达REIC/Dkk-3诱导睾丸生殖细胞癌细胞系NCCIT中的凋亡，但不诱导正常人成纤维细胞中的凋亡。c-Jun末端激酶（JNK）被Ad-REIC激活，JNK抑制剂可阻断JNK诱导的细胞凋亡。单次瘤内注射Ad-REIC可明显抑制NCCIT细胞在裸鼠体内的成瘤生长。这些结果表明，Ad-REIC可能导致开发针对人类睾丸癌的较少侮辱性和非遗传毒性的治疗措施。
Human testicular cancer is very sensitive to chemotherapy and radiation therapy and is regarded as a curable cancer. The cancer prevails in the young reproductive generation and testicular dysfunction is often observed as a side effect, remaining a serious challenge. In the present study, we examined the potential utility of REIC/Dkk-3-based gene therapy against human testicular cancer. Expression of REIC/Dkk-3 was reduced in all of the human seminoma and non-seminomatous germ cell tumor tissues. Overexpression of REIC/Dkk-3 using an adenovirus vector (Ad-REIC) induced apoptosis in a testicular germ cell cancer cell line NCCIT but not in normal human fibroblasts. c-Jun terminal kinase (JNK) was activated by Ad-REIC and the induction of apoptosis was abrogated by a JNK inhibitor. A single intratumoral injection of Ad-REIC markedly inhibited the tumorigenic growth of NCCIT cells in nude mice. These results indicate that Ad-REIC may lead to developing less insulting and non-genotoxic therapeutic measures against human testicular cancer.